This revised proposal concerns further development of knowledge on the interaction of mycoplasmas (mollicutes) and eukaroytic cells, using techniques that measure cytadherence and intracellular invasion of three important Mycoplasma species of man (M. penetrans, M. genitalium, and M. pneumoniae) to selected target mammalian cells. As an extension of the group's earlier studies on mycoplasmal adherence and pathogenicity, the research strategy will involve application of a variety of microscopic techniques, cellular fractionation, fluorescence- labeling and cell sorting, and other biochemical, immunological, and genetic approaches to define the events following mollicute adherence and intracellular invasion. The availability of various mutant strains of the three Mycoplasma species, deficient in such selected properties as cytadherence and intracellular invasion, offers a unique avenue to clarify specific mechanisms of mycoplasmal pathogenesis, including key alterations in cell structure and function and other molecular events relevant to understanding immunologic and cellular manifestations of human mycoplasmal disease.